A Study to Evaluate the Efficacy of Osimertinib With Early Intervention SRS Treatment Compared to the Continuation of Osimertinib Alone, in Patients With EGFR Mutated NSCLC and Asymptomatic Brain Metastases

August 30, 2021 updated by: Meirrovitz Amichay, Hadassah Medical Organization

A Multi-center, Open-label, Randomized, Two-arm Study, to Evaluate the Efficacy of Osimertinib With Early Intervention SRS Treatment Compared to the Continuation of Osimertinib Alone, in Patients With EGFR Mutated NSCLC and Asymptomatic Brain Metastases.

This study involves patients with EGFR-mutated NSCLC and asymptomatic brain metastases. This is an open-label, randomized study, comparing the continuation of Osimertinib treatment alone to Osimertinib treatment combined with early intervention stereotactic radiosurgery (SRS). The current first line of care for EGFR-mutated NSCLC is administration of Osimertinib, a small molecule that penetrates the blood brain barrier (BBB) well and controls majority, but not all, of the brain metastases. We hypothesize that relatively early intervention with SRS to brain metastases that are still visualized by MRI 2 months-post initiation of Osimertinib treatment, LUNG- will improve long term brain control, cognitive abilities and potentially overall survival. Patients with EGFR-mutated NSCLC and asymptomatic brain metastases will be treated with Osimertinib for 2 months. Brain MRI scans will be collected pre-Osimertinib and 2 months after treatment start. Patients with asymptomatic brain metastases present after 2 months of Osimertinib will be randomized into one of two study arms. Arm A patients will be treated with SRS while continuing Osimertinib, while arm B patients will continue with Osimertinib alone. Patients will be assessed based on brain and whole body progression by RECIST. Patients will also be assessed for CNS-PFS and body-PFS, cognitive function, Quality of life and overall survival status via routine follow-up tests.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

162

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Newly diagnosed metastatic NSCLC, not amenable to curative surgery or curative radiotherapy.
  2. Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be sensitive to Osimertinib - These include exon 19 del; L858R (exon 21); G719X (exon 18); L861G (exon 21); S768I (exon 20) and T790M (exon 20) NOTE: Mutation analysis is to be done as per local practice.
  3. An MRI showing brain metastases. At randomization, number of brain lesions is under 20. Patients with over 20 brain lesions at randomization MRI will be suitable for whole brain radiation, and will not be randomized.
  4. Brain metastases are asymptomatic or with minor symptoms (ECOG≤2) at study randomization.
  5. ECOG performance status ≤2 and a minimum life expectancy of at least 6 months
  6. Must be eligible and receive Osimertinib as their anti EGFR TKI at time of randomization.
  7. Must be eligible for SRS treatment at time of randomization.
  8. Provided written informed consent.
  9. Be male or female and at least 18 years of age on the day of signing informed consent.

  10. Female patients:

    1. Willing to use adequate contraceptive measures until 6 weeks after the final dose of study treatment
    2. Not breast feeding
    3. Have a negative pregnancy test prior to the start of dosing if of childbearing potential or have evidence of non-childbearing potential by fulfilling one of the following criteria at screening:
    4. Post-menopausal, defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments ii. Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels in the post-menopausal range for the institution iii. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
  11. Male patients who are willing to use barrier contraception (i.e. condoms) until 4 months after the final dose of study treatment.

Exclusion Criteria:

  • a. Prior treatment with:

    1. Anti EGFR TKI treatment.
    2. Checkpoint inhibitors immunotherapy for metastatic NSCLC.
    3. Whole brain radiation (WBRT) and/or Stereotactic Radiosurgery (SRS).
    4. Medications or herbal supplements known to be potent inducers of CYP3A4 and are unable to stop use within the recommended wash out period prior to receiving the first dose of Osimertinib.
    5. An investigational drug within five half-lives of the compound.

    6. Any other cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of entry to the study.

      b. Systemic progression under Osimertinib treatment between screen and randomization systemic scan, per RECIST1.1.

      c. Spinal cord compression unless asymptomatic and stable. d. Leptomeningeal disease. e. Moderate or severe symptomatic brain metastases defined as per Radiation Therapy Oncology Group acute morbidity grade 3 to 4.

      NOTE: Grade 3 refers to neurological findings requiring hospitalization for initial management. Grade 4 refers to serious neurological impairment including paralysis, coma or seizures more than three times per week despite medication and requires hospitalization.

      f. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.

      g. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of Osimertinib.

      h. Involvement in the planning and conduct of the study i. Judgement by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Early SRS treatment with SoC
Stereotactic surgery (SRS) to the brain metastases and continuation of Osimertinib, at 2 month (8 weeks) post Osimertinib start
Radiation: Stereotactic surgery
At two month (8 weeks) post Osimertinib start, patients will be randomized into one of the two study arms. Arm A patients will be treated with stereotactic surgery (SRS). In both arms Osimertinib treatment will continue.
Active Comparator: SoC Tagrisso treatment only
continuation of osimertinib alone
Radiation: Stereotactic surgery
At two month (8 weeks) post Osimertinib start, patients will be randomized into one of the two study arms. Arm A patients will be treated with stereotactic surgery (SRS). In both arms Osimertinib treatment will continue.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brain control: CNS-PFS
Time Frame: Change in lesion size in the CNS will be followed and assessed at screen, Randomization, 2 month after Randomization, then every 3 month
Lesions that did not disappear after two months of Osimertinib treatment will be better controlled with SRS
Change in lesion size in the CNS will be followed and assessed at screen, Randomization, 2 month after Randomization, then every 3 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
whole body PFS
Time Frame: Change in lesion size in the whole body will be followed and assessed at screen, Randomization, 2 month after Randomization, then every 3 month
Whole body progression will be delayed when Osimertinib is combined with early treatment of SRS
Change in lesion size in the whole body will be followed and assessed at screen, Randomization, 2 month after Randomization, then every 3 month
Cognitive function
Time Frame: Change in patient cognitive function will be followed and assessed at screen, Randomization, 2 month after Randomization, then every 3 month
Patient cognitive function will improve after SRS treatment
Change in patient cognitive function will be followed and assessed at screen, Randomization, 2 month after Randomization, then every 3 month
Quality of life (QOL)
Time Frame: Change in patient quality of life will be followed and assessed at screen, Randomization, 2 month after Randomization, then every 3 month
Patient QOL will improve after SRS treatment
Change in patient quality of life will be followed and assessed at screen, Randomization, 2 month after Randomization, then every 3 month
Time to whole brain radiation
Time Frame: Status will be checked at every visit and follow up
Time until whole brain radiation will be given will prolong for patients who receive early SRS treatment
Status will be checked at every visit and follow up
Overall survival (OS)
Time Frame: Status will be checked at every visit and follow up
Patient OS will improve after SRS treatment
Status will be checked at every visit and follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hadassah Medical Organization

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 9, 2021

Primary Completion (Anticipated)

December 31, 2024

Study Completion (Anticipated)

December 31, 2026

Study Registration Dates

First Submitted

July 4, 2021

First Submitted That Met QC Criteria

August 30, 2021

First Posted (Actual)

September 5, 2021

Study Record Updates

Last Update Posted (Actual)

September 5, 2021

Last Update Submitted That Met QC Criteria

August 30, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LUNG-OSIME-SRS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD Plan Description

Data for individual participants will be collected anonymously via the study CRF, data will be analyzed statistically and published.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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